The mediating effect of blood pressure between healthy lifestyles and stroke: Results from the China Kadoorie Biobank study

Abstract

While a healthy lifestyle is known to reduce the risk of stroke, the extent to which blood pressure (BP) mediates this association remains unclear. The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence. Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline, we employed structural equation modeling to assess the mediating effects of systolic (SBP) and diastolic (DBP) blood pressure. During the follow-up, 2811 incident stroke cases were identified. A healthy lifestyle was significantly associated with a reduced risk of stroke, with SBP mediating 44.70% (β = −0.0014, 95% confidence interval [CI]: −0.0016 to −0.0012) and DBP mediating 37.81% (β = −0.0012, 95% CI: −0.0015 to −0.0009) of this association. The mediating effects were attenuated but remained significant for ischemic stroke (SBP: 33.21%; DBP: 27.24%). In conclusion, approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP. These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.

Keywords

stroke / blood pressure / lifestyle / mediation analysis

Funding

This work was supported by the Jiangsu Provincial Health Commission Medical Research Project (Grant Nos. K2024081 to R.T. and BJ23027 to J.S.).

Acknowledgments

We thank the Chinese Center for Disease Control and Prevention, the Chinese Ministry of Health, and the National Health and Family Planning Commission of China. The most important acknowledgment is extended to the participants in the study and the members of the survey teams in the Suzhou regional center, as well as to the project development and management teams based in Beijing and Oxford. The baseline survey and long-term follow-up of the China Kadoorie Biobank (CKB) project were supported by grants from the National Natural Science Foundation of China (Grant Nos. 82192900, 82192901, 82192904, 81390540, and 91846303 to L.L.), the National Key Research and Development Program of China (Grant No. 2016YFC0900500 to Y.G.), the Kadoorie Charitable Foundation in Hong Kong, and the Wellcome Trust in the UK (Grant/Award Nos. 088158/Z/09/Z, 104085/Z/14/Z, and 202922/Z/16/Z to Z.C.).

Additional information

The online version contains supplementary material available at http://www.jbr-pub.org.cn/article/doi/10.7555/JBR.39.20250177?pageType=en.

References

[1] Ma Q, Li R, Wang L, et al. Temporal trend and attributable risk factors of stroke burden in China, 1990-2019: An analysis for the Global Burden of Disease Study 2019[J]. Lancet Public Health, 2021, 6(12): e897-e906. doi: 10.1016/S2468-2667(21)00228-0

[2] Lv J, Yu C, Guo Y, et al. Adherence to healthy lifestyle and cardiovascular diseases in the Chinese population[J]. J Am Coll Cardiol, 2017, 69(9): 1116-1125. doi: 10.1016/j.jacc.2016.11.076

[3] Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines[J]. Circulation, 2018, 138(17): e426-e483. doi: 10.1161/CIR.0000000000000597

[4] Wang JG. Chinese Hypertension Prevention and Treatment Guidelines Revision Committee. Chinese Guidelines for the Prevention and Treatment of Hypertension (2024 revision)[J]. J Geriatr Cardiol, 2025, 22(1): 1-149. doi: 10.26599/1671-5411.2025.01.008

[5] Yang X, Li J, Hu D, et al. Predicting the 10-year risks of atherosclerotic cardiovascular disease in Chinese population: The China-PAR Project (Prediction for ASCVD Risk in China)[J]. Circulation, 2016, 134(19): 1430-1440. doi: 10.1161/CIRCULATIONAHA.116.022367

[6] Valenzuela PL, Carrera-Bastos P, Gálvez BG, et al. Lifestyle interventions for the prevention and treatment of hypertension[J]. Nat Rev Cardiol, 2021, 18(4): 251-275. doi: 10.1038/s41569-020-00437-9

[7] Rutten-Jacobs LC, Larsson SC, Malik R, et al. Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: Cohort study of 306 473 UK Biobank participants[J]. BMJ, 2018, 363: k4168. doi: 10.1136/bmj.k4168

[8] Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: A systematic review and meta-analysis[J]. Lancet, 2016, 387(10022): 957-967. doi: 10.1016/S0140-6736(15)01225-8

[9] Yang S, Han Y, Yu C, et al. Development of a model to predict 10-year risk of ischemic and hemorrhagic stroke and ischemic heart disease using the China Kadoorie Biobank[J]. Neurology, 2022, 98(23): e2307-e2317. doi: 10.1212/WNL.0000000000200139

[10] Chen Z, Chen J, Collins R, et al. China Kadoorie Biobank of 0.5 million people: Survey methods, baseline characteristics and long-term follow-up[J]. Int J Epidemiol, 2011, 40(6): 1652-1666. doi: 10.1093/ije/dyr120

[11] Du H, Bennett D, Li L, et al. Physical activity and sedentary leisure time and their associations with BMI, waist circumference, and percentage body fat in 0.5 million adults: The China Kadoorie Biobank study[J]. Am J Clin Nutr, 2013, 97(3): 487-496. doi: 10.3945/ajcn.112.046854

[12] Qin C, Guo Y, Pei P, et al. The relative validity and reproducibility of food frequency questionnaires in the China Kadoorie Biobank study[J]. Nutrients, 2022, 14(4): 794 doi: 10.3390/nu14040794

[13] Su J, Geng H, Chen L, et al. Association of healthy lifestyle with incident cardiovascular diseases among hypertensive and normotensive Chinese adults[J]. Front Cardiovasc Med, 2023, 10: 1046943. doi: 10.3389/fcvm.2023.1046943

[14] Qin C, Lv J, Guo Y, et al. Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults[J]. Heart, 2018, 104(21): 1756-1763. doi: 10.1136/heartjnl-2017-312651

[15] Du H, Li L, Bennett D, et al. Fresh fruit consumption and major cardiovascular disease in China[J]. N Engl J Med, 2016, 374(14): 1332-1343. doi: 10.1056/NEJMoa1501451

[16] Wang S, Lay S, Yu H, et al. Dietary Guidelines for Chinese Residents (2016): Comments and comparisons[J]. J Zhejiang Univ Sci B, 2016, 17(9): 649-656. doi: 10.1631/jzus.B1600341

[17] Wang M, Gong W, Hu R, et al. Associations between stressful life events and diabetes: Findings from the China Kadoorie Biobank study of 500000 adults[J]. J Diabetes Investig, 2019, 10(5): 1215-1222. doi: 10.1111/jdi.13028

[18] American Diabetes Association. Diagnosis and classification of diabetes mellitus[J]. Diabetes Care, 2014, 37(S1): S81-S90. doi: 10.2337/dc14-S081

[19] Zhou J, Zhou L. Comprehensive nursing model for diabetic foot ulcers: A strategy to improve prognosis and quality of life[J]. Medicine (Baltimore), 2024, 103(26): e38674. doi: 10.1097/MD.0000000000038674

[20] Robins JM, Hernán MÁ, Brumback B. Marginal structural models and causal inference in epidemiology[J]. Epidemiology, 2000, 11(5): 550-560. doi: 10.1097/00001648-200009000-00011

[21] Gunzler D, Chen T, Wu P, et al. Introduction to mediation analysis with structural equation modeling[J]. Shanghai Arch Psychiatry, 2013, 25(6): 390-394. doi: 10.3969/j.issn.1002-0829.2013.06.009

[22] Chiuve SE, Rexrode KM, Spiegelman D, et al. Primary prevention of stroke by healthy lifestyle[J]. Circulation, 2008, 118(9): 947-954. doi: 10.1161/CIRCULATIONAHA.108.781062

[23] Conklin DJ, Schick S, Blaha MJ, et al. Cardiovascular injury induced by tobacco products: Assessment of risk factors and biomarkers of harm. A Tobacco Centers of Regulatory Science compilation[J]. Am J Physiol Heart Circ Physiol, 2019, 316(4): H801-H827. doi: 10.1152/ajpheart.00591.2018

[24] Husain K, Ferder L, Ansari RA, et al. Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats[J]. Hum Exp Toxicol, 2011, 30(8): 930-939. doi: 10.1177/0960327110384520

[25] Wang X, Carcel C, Woodward M, et al. Blood pressure and stroke: A review of sex- and ethnic/racial-specific attributes to the epidemiology, pathophysiology, and management of raised blood pressure[J]. Stroke, 2022, 53(4): 1114-1133. doi: 10.1161/STROKEAHA.121.035852

[26] Pessôa BS, Slump DE, Ibrahimi K, et al. Angiotensin Ⅱ type 2 receptor- and acetylcholine-mediated relaxation: Essential contribution of female sex hormones and chromosomes[J]. Hypertension, 2015, 66(2): 396-402. doi: 10.1161/HYPERTENSIONAHA.115.05303

[27] Gillis EE, Sullivan JC. Sex differences in hypertension: Recent advances[J]. Hypertension, 2016, 68(6): 1322-1327. doi: 10.1161/HYPERTENSIONAHA.116.06602

[28] Ahmed Z, Chaudhary F, Agrawal DK. Epidemiology, pathophysiology, and current treatment strategies in stroke[J]. Cardiol Cardiovasc Med, 2024, 8(4): 389-404. doi: 10.26502/fccm.92920399

[29] Zhang H, He M, Zhang X. Association of lifestyle change with incident stroke and its subtypes[J]. Chin J Dis Control Prev, 2021, 25(3): 259-265. doi: 10.16462/j.cnki.zhjbkz.2021.03.003

[30] Han Y, Hu Y, Yu C, et al. Lifestyle, cardiometabolic disease, and multimorbidity in a prospective Chinese study[J]. Eur Heart J, 2021, 42(34): 3374-3384. doi: 10.1093/eurheartj/ehab413